CADD approaches

This article will provide a brief introduction to computational chemistry, molecular modeling, and CADD theory. Clearly, it is impossible to cover in this short review all of the useful and/or interesting CADD approaches. Although this is relatively a new field of research, there are many examples from which to... 

The following Figure 3.13 illustrates a typical flowchart used by drug-discovery researchers by making uses of a variety of known CADD approaches. 

Structure-based molecular design, computer-aided molecular design (CAMD), computer-aided drug design (CADD), approaches for lead structure identification and optimization in the drug development process. The rational design of a lead structure in drug development basically relies upon the three-dimensional structure of... 

Wermuth, C. G., The impact of QSAR and CADD methods in drug design. In Rational Approaches to Drug Design, Hoeltje, H.D., Sippl, W. (eds.). Prous Science, Barcelona, 2001, pp. 3-20. 

Novel approaches to hioanalysis and testing (e.g. LOC, biochip and POCT) coupled with advances in CADD, genomics and proteomics should help realize the ultimate goal of personalized medicine. 

The term CADD has been used to describe two aspects of the recent use of computational tools that aid computational and medicinal chemists in the search for new drug candidates. In the first approach, medicinal chemists attempt to describe the predominant statistical correlation of biological activity with directly measurable physicochemical parameters or characteristics of drugs and is known as Quantitative Structure-Activity Relationships (QSAR). The central idea is that compounds exhibit biological activity based on structural characteristics. It should then be possible to correlate the associated biological activity with various critical parameters. Ingeneral, the biological activity may be considered a function of hydropho-bicity, electrostatics, and steric forces [Eq. (18)]. 

Success stories that demonstrated the capabilities of both approaches in the CADD technique have been described in Table 5. 

Until all-electron, ab initio CADD arrives, we can use DFT to examine smaller drug-protein complexes and to validate current scoring functions in order to determine the best way to move forward. This review will discuss some basic DFT formalism, explore current approaches in DFT that are likely to lead to methods appropriate for drug-protein systems, and discuss some recent applications of DFT to ligand-protein interactions. 

It was also clear that calculation of log Poet for the immense variety of structures that might be considered in computer-assisted drug design (CADD) would be impractical based on the 7i-system, and thus fragmental and whole molecule approaches have dominated these calculations. Since it plays such a pivotal role in the Hammett-Hansch QSAR methodology, the basis for log Poet calculation will be examined in some detail because, even though they lack a firm, theoretical basis, the calculation details can often be as useful in CADD as the bottom line number. 

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